Genetic and biochemical studies with enterobacteria suggest that the regulation of nitrogen metabolism in these organisms is quite complex. The NH3-assimilatory enzymes, as well as some amino acid transport systems and catabolic enzymes, appear to be involved in the process. Because of its unique biochemical properties and its important role in nitrogen metabolism, glutamine synthetase is of primary interest. The purpose of this work is to study, via genetic and biochemical techniques, the mechanism by which the synthesis of glutamine synthetase is controlled in Escherichia coli K12. Special attention is focused on identifying the elements of this control and on determining whether they are specific for the regulation of glutamine synthetase or whether they might represent effectors in the regulation of the class of NH3-assimilatory enzymes within the general scheme for nitrogen control.